Lecture 3 - Macrocytic Anemia Flashcards
MCV >100?
Macrocytic anemia
Basic mechanism of anemia? (Causes)
RBC disruption
- dietary deficiency
- abnormal metabolism of B12/folate
- ineffective erythropoiesis
If MCV > 100 you need to test for?
B 12
Folate
MCV >100 with
- Low vitamin B12
What may cause this?
Megaloblastic anemai (pernicious anemia)
Think:
- dietary deficiency
- GI disease
- Post-gastrectomy
MCV >100 with:
- low folate?
What may cause this?
Megaloblastic anemia
Dietary deficiency
GI disease
MCV > 100 with:
- normal B12 and folate?
Liver diseases
Myelodysplastic syndrome
Reticulocytosis
Common causes of macrocytosis.
Its a long list, dont memorize it
DNA metabolism
- B12
- folate
- Drugs
- Hydroxuriea
- methotrexate
Shift to immature or stressed RBC
- reticulocytosis
- aplastic anemia
Primary bone marrow disorder
- myelodysplastic syndromes
Liver abnormalities
- liver disease
- hypothyroidism
- hyperlipidemia
MOA ukn
- ETOH
Pt has macrocytic anemia with normal B12 and folate
You find Hypersegmented neutrophils on peripheral smear
Strongly suggest megalobastic anemia
Pt has macrocytic anemia with normal B12 and folate
No nutritional or drug induced cause.
Look at how high the MCV is
100:
> 105:
100
- hypothyroidism,
- pregnancy,
- liver disease,
- ETOH
> 105: bone marrow d/o (MDS)
- late megalobastic anemia
- pernicious anemia
Common social causes of macrocytic?
ETOH
Drugs
Macrocytic anemia iwth microcytes and macrocytes on peripheral smear
Pt has coexisting condition probably:
- IDA
- Thalassemia
What is megaloblastic anemia?
A type of macrocytic anemia
A group of blood disorders that share common morphological characteristics (large, atypical)
MC cause of megalobastic anemia?
B12 and folic acid deficiency (usually intake problem, looking at you jake)
What do folate and B12 do for the body?
Purine synthesis and subsequent DNA synthesis
- leads to abnormal erythropoiesis
What is the biggest concern for untreated B12 deficiency?
Neuropsychiatric symptoms (late sign)
B12 deficiency essentials of diagnosis?
- MCV > 100
- Macro-ovalocyutes and hypersegmented neutrophils
- serum B12 low
- <170g/mL (low)
- 200-300 (borderline)
If B12 is 200-300 order?
MMA (methylmalonic acid)
Homocysteine
Why High MMA with low b12?
B12 is a cofactor in conversion of methylmalonyl-CoA succinyl-CoA in the mitochondria
Thus low B12 leads to accumulation of MMA
Where does B12 come from?
Animals
How much B12 do we store and use? How long can we go w/ out it?
Liver stores 2000-5000mcg
Daily use is 3-5mcg
You have approx 3 yrs till you need more
Cause of B12 deficiency?
Strict Vegans
Abdominal surgery
Rare causes
- fish tapeworm
- severe crohn’s
Clinical findings of B12 deficiency?
Megaloblastic anemia - Fatigue, palor, malaise, SOB HCT < 10-15% Changes in mucosal cells - glossitis, Gi complaints
Neuropsychiatric symptoms
Describe neuropsychatric symptoms
Peripheral nerves first -> paresthesias
Balance problems -> ataxia
Cerebral function leading to dementia (late)
What are the 2 steps required for the body to absorb b12?
- Hydrochloric acid separates b12 from carier protein
2. B12 combines w IF for absorption in TERMINAL ILEUM
Pts with Pernicious Anemia have? (Causes)
Antibody to IF or parietal cells
Parietal cells are the site of production of IF
What does folate (b9) do in the body?
It is a co-factor in cellular reactions, but does not participate in methylmalonic acid metabolism (MMA)
- so normal MMA on labs
Sources of B9?
Fruits (citrus)
Green leafy vegetables
What is entherohepatic recirculation?
One of 2 methods for absorption of B9 (folate)
The B9 rides the bile train back into the intestine
The other method is normal absorption
Storage and use of B9?
Store about 5000 mcg
You use lots of it so you only have weeks to months worth of supply
What is a “dual deficiency” (folate deficiency)
Caused by ETOH abuse
- interferes w initial absorption
- f’s with enterohepatic circulation
Causes of folate deficiency?
Nutritional causes
Increased requirements (pregg)
Malabsorptive causes (rare but may be GI or drugs)
What drugs are associated w B9 deficiency?
ETOH (its medicine, dont judge me)
Methotrexate Sulfasalazine (ASA derivative) Triamterene (K sparing diuretic) Pyrimethamine (antiparasitic) Trimethoprim/sulfam ethozazole Diphenylhydatoin (phenytoin) Barbituates Topiramate Hydroxyurea
What is different about ETOH, topiramate, and hydroxyurea induced anemia?
They cause drug-induced macrocytic anemia with or without interfering w folate
Clinical features of B12 and folate (list)
Hematologic Cardiopulmonary GI Derm Genial Reproductive Psych NEUROPSYCHIATRIC (B12 specific)
See slide 29 for more in depth stuff
One more time, what blood work is required for DX of megaloblastic anemias?
Direct B12 and folate - B12 <170pg/mL - B9 < 150ng/mL Homocysteine level MMA
Tx of asymptomatic B12 macrocytic anemia or b12 deficiency induced peripheral neuropathy
B12
PO: 1000mcg daily
Or
IM: 1000 mcg once monthly
If asymptomatic
TX for perinicious anemia and neurological dysfunction?
You win shots for life (must be parenteral)
1000mcg IM daily x 1 week, then weekly x 4 weeks, then monthly x life
Tx for neurologic dysfunction only
B12 - Can take PO once initial deficiency has been corected and pt is asymptomatic
Folate
How fast do you see improvement when treating B12?
Erythropoiesis starts to normalize w/in 1-2 days
Hypersegmented neutrophils get better in 10-14 days
How to treat folate deficiency?
Oral B9
1mg PO daily x 1-4 months or until mo-better
Why does liver disease cause macrocytic anemia?
It impairs lipid metabolism
- we think excess lipids are deposited in RBC lipid bilayer resulting in increased size (macrocytosis)
Beside absorption why does ETOH cause macrocytic anemia?
Direct bone marrow toxicity
Abnormal RBC lipid metabolism (like liver disease)
Interferes w folate metabolism
Will alcohol induced macrocytic anemia get better?
Usually w/in 2-4 months of abstinence if irreversible damage has not occurred
Myelodysplastic syndrome s (MDS) is aka?
Pre-leukemia
What is myelodysplastic syndrome (MDS)?
Heterogeneous bone marrow disorders characterized by ineffective blood cell production and dysplasia due to mutation in a hematopoietic stem cell
What causes MDS?
Primary: idiopathic
Secondary: med treatments
- chemo
- radiation therapy
- toxic substances (benzene)
MDS clinical features?
- Hematologic (MCV 105+) (cytopenias)
- increased risk of AML (leukemia) (roughly 30% get this)
- present w fatigue, infection or bleeding
- indolent presentation (wasting, fever)
- +/- splenomegaly
MDS diagnosis?
Cytopenia w hypercellular bone marrow
Morphologic abnormalities in 2 or more hematopoietic cell lines
Get a bone marrow biopsy
MDS tx?
No single therapy
- transfusions
- hematologic stimulating factors
- bone marrow transplant
- experimental shit (chemo, immunosuppression etc)
Marked reticulocytosis?
MCV spuriously increased when there are excessive reticulocytes in the peripheral blood. Usually transiently observed in patients with massive hemolysis without a coexisting microcytic process
Hypothyroidism?
Mechanisms unknown.
Hypothyroid patients should also be evaluated for pernicious anemia due to chronic autoimmune thyroiditis
Pregnancy for other macrocytic ?
INCREASED folate requirements may account for mild macrocytosis which is rarely OVer 100. Folate supplementaiton during pregnancy also significantly reduces risk of neural tube defects in child.
Um, no mr vance
AB caffeinated is not a blood type
